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Could we have a SENS proof of concept therapy ready for the lab by the end of the decade?

sens stem cells senolytic advanced glycation endproducts

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#1 corb

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Posted 29 March 2015 - 03:24 PM


In light of a couple of articles and studies from the last months I've started to wonder if SENS couldn't do a preliminary investigation into their proposed therapies very soon.

 

Quercetin seems to spur senescent cells into death but is also a known inhibitor of AGEs formation, possibly the best one readily available and better than some experimental substances like aminoguanidine. A liposome or micele formulation of quercetin increases it's bioavailability in an experimental setup. Dasatinib and potentially some other cancer drugs have a similar effect.

 

Certain types of stem cell therapies are readily available, specifically mesenchymal and hematopoetic.

In experiment mesenchymal stem cells are capable of transferring mitochondria to cells with disturbed mitochondrial functions (but unfortunately not to ones with mtDNA mutations).

 

There are already some drugs capable of affecting the extra cellular matrix. In combination with quercetin they should give a good intermediate avenue for development in the short term. Furthermore a human engineered skin model was developed recently and that should sufficiently speed up the research from now on.

 

Last year a team of scientist successfully lowered the amount of lipofuscin from macular tissues with beta cyclodextrins.

 

So let's review what we have:

  1. A somewhat working therapy for senescent cells
  2. A method for inhibiting the formation of AGEs and in the last case scenario the ability to slightly remodel the extra cellular matrix
  3. Stem cell therapies
  4. which have an observed benefit for mitochondria as well
  5. A reagent capable of instigating a removal of some lipofuscin from cells

None of those are perfect or "complete" but they work well enough in the lab and right now a good result in the labs could go a long way both for changing the public opinion and the opinion of the medical community. And we still don't have a robust anti cancer treatment BUT the experiment could simply use a species with a low propensity to developing cancers - so rodents are potentially out of the question.

 

What do you think?



#2 alc

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Posted 30 March 2015 - 11:18 PM

Here is my take on this subject:

End of this century is a long way. Just look at how this field (counteracting + reversing aging) changed (in good) for past ten years. Imagine what will hapen in 20 and then in 30 years, so the rational answer is yes, it will happen (sooner). But my simple guess is (even I support SENS by donating) that others will leapfrog them and reach to the goal. That is because SENS lacks basic/essential marketing skills. Also they doesn't show any intention of completing their research work. They just want to do the "theoretical" part and have others picking up and bring it in humans. That is plain wrong. SENS needs to capitalize in every single good work that they are part of it.

And now becoming negative, if you watch de Grey's interviews, they haven't changed much for past 6 years or so. He is using same numbers same analogies, same complains. He gives in his interviews "50/50 chance" that in "next 20-25 years" will happen (with appropriate funding). So, if I'm a person that have no idea what they do and watch an interview with him from 5 years ago and watch one of the recent, I'll say in my head: "five years ago, 50/50 chance, now five years after same 50/50 chance. So there is no progress at all. By extrapolation, in 25 years situation will be the same". He really needs to be more marketing oriented - or leave other people do that for SENS. Just that way they can attract necessary funds. Let's hope SENS understand where they need to change and improve and will pick up pace in their work. We all want them to succeed, just that good scientists need help from marketing people to sell their work and bring in so much needed funding.


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#3 Kalliste

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Posted 31 March 2015 - 05:37 AM

Did you mean decade and not century corb? I'm also think down along these lines. We have a lot of good looking stuff right now. I wish a Bill Gates or Mark Zuckenberg would step in and fund a dozen trials of the stuff that seems to work right now.



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#4 corb

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Posted 31 March 2015 - 12:29 PM

Did you mean decade and not century corb? I'm also think down along these lines. We have a lot of good looking stuff right now. I wish a Bill Gates or Mark Zuckenberg would step in and fund a dozen trials of the stuff that seems to work right now.

 

Yes I did mean by the end of the decade. That's a very annoying mistake, I should contact a moderator to change the title of the thread. It changes the meaning completely.

 

 

Here is my take on this subject:

End of this century is a long way. Just look at how this field (counteracting + reversing aging) changed (in good) for past ten years. Imagine what will hapen in 20 and then in 30 years, so the rational answer is yes, it will happen (sooner). But my simple guess is (even I support SENS by donating) that others will leapfrog them and reach to the goal. That is because SENS lacks basic/essential marketing skills. Also they doesn't show any intention of completing their research work. They just want to do the "theoretical" part and have others picking up and bring it in humans. That is plain wrong. SENS needs to capitalize in every single good work that they are part of it.

And now becoming negative, if you watch de Grey's interviews, they haven't changed much for past 6 years or so. He is using same numbers same analogies, same complains. He gives in his interviews "50/50 chance" that in "next 20-25 years" will happen (with appropriate funding). So, if I'm a person that have no idea what they do and watch an interview with him from 5 years ago and watch one of the recent, I'll say in my head: "five years ago, 50/50 chance, now five years after same 50/50 chance. So there is no progress at all. By extrapolation, in 25 years situation will be the same". He really needs to be more marketing oriented - or leave other people do that for SENS. Just that way they can attract necessary funds. Let's hope SENS understand where they need to change and improve and will pick up pace in their work. We all want them to succeed, just that good scientists need help from marketing people to sell their work and bring in so much needed funding.

 

There's a number of reasons I can think off for SENS to not want to capitalize on their research.

Distinguishing them from previous endeavors. Ones which started capitalizing before they had anything to capitalize. And there's a lot of those unfortunately.

The other reason is, if it's free knowledge everyone can pick it up and extrapolate from it. Which is important because one group (or five for that matter) of scientists can't possibly finish this research in a meaningful time frame.
 

 



#5 Kalliste

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Posted 31 March 2015 - 01:03 PM

Another thing I have been pondering is the use of nanoparticles.

We have seen positive reports for a number of things:

 

Nanomedicine. 2015 Feb 11. pii: S1549-9634(15)00037-4. doi: 10.1016/j.nano.2015.01.013. [Epub ahead of print]
Bioactive silica nanoparticles reverse age-associated bone loss in mice.
Author information
  • 1The Atlanta Department of Veterans Affairs Medical Center, Decatur, GA, USA; Emory University, Department of Medicine, Division of Endocrinology, Atlanta, GA, USA; The Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA. Electronic address: mweitzm@emory.edu.
  • 2Emory University, Department of Medicine, Division of Endocrinology, Atlanta, GA, USA.
  • 3The Atlanta Department of Veterans Affairs Medical Center, Decatur, GA, USA; Emory University, Department of Medicine, Division of Endocrinology, Atlanta, GA, USA.
  • 4Department of Chemistry, Seoul National University, Seoul, Republic of Korea.
  • 5The Atlanta Department of Veterans Affairs Medical Center, Decatur, GA, USA; Emory University, Department of Medicine, Division of Endocrinology, Atlanta, GA, USA; The Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA. Electronic address: george.beck@emory.edu.
Abstract

We recently reported that in vitro, engineered 50nm spherical silica nanoparticles promote the differentiation and activity of bone building osteoblasts but suppress that of bone-resorbing osteoclasts. Furthermore, these nanoparticles promote bone accretion in young mice in vivo. In the present study the capacity of these nanoparticles to reverse bone loss in aged mice, a model of human senile osteoporosis, was investigated. Aged mice received nanoparticles weekly and bone mineral density (BMD), bone structure, and bone turnover were quantified. Our data revealed a significant increase in BMD, bone volume, and biochemical markers of bone formation. Biochemical and histological examinations failed to identify any abnormalities caused by nanoparticle administration. Our studies demonstrate that silica nanoparticles effectively blunt and reverse age-associated bone loss in mice by a mechanism involving promotion of bone formation. The data suggest that osteogenic silica nanoparticles may be a safe and effective therapeutic for counteracting age-associated bone loss.

Copyright © 2015. Published by Elsevier Inc.

 

 

http://www.ncbi.nlm....pubmed/25680544

 

 

 

Cerium oxide nanoparticles (nanoceria) are widely used in a variety of industrial applications including UV filters and catalysts. The expanding commercial scale production and use of ceria nanoparticles have inevitably increased the risk of release of nanoceria into the environment as well as the risk of human exposure. The use of nanoceria in biomedical applications is also being currently investigated because of its recently characterized antioxidative properties. In this study, we investigated the impact of ceria nanoparticles on the lysosome-autophagy system, the main catabolic pathway that is activated in mammalian cells upon internalization of exogenous material.

We tested a battery of ceria nanoparticles functionalized with different types of biocompatible coatings expected to have minimal effect on lysosomal integrity and function. We found that ceria nanoparticles promote activation of the transcription factor EB, a master regulator of lysosomal function and autophagy, and induce upregulation of genes of the lysosome-autophagy system. We further show that the array of differently functionalized ceria nanoparticles tested in this study enhance autophagic clearance of proteolipid aggregates that accumulate as a result of inefficient function of the lysosome-autophagy system.

This study provides a mechanistic understanding of the interaction of ceria nanoparticles with the lysosome-autophagy system and demonstrates that ceria nanoparticles are activators of autophagy and promote clearance of autophagic cargo. These results provide insights for the use of nanoceria in biomedical applications, including drug delivery. These findings will also inform the design of engineered nanoparticles with safe and precisely controlled impact on the environment and the design of nanotherapeutics for the treatment of diseases with defective autophagic function and accumulation of lysosomal storage material.

https://www.fightagi...e-autophagy.php

 

And of course our beloved C60 lipofullerenes.

 

Maybe these substances could be combined to an actual anti-aging cocktail.



#6 Kalliste

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Posted 31 March 2015 - 03:31 PM

There was this little item on Fightaging today:

http://www.longecity...ation/?p=721392

 

Maybe I'm getting a bit carried away but it really seems we are approaching a time when we can start talking about LEV for real. These treatments are inching ever closer to repair status.

 



#7 corb

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Posted 31 March 2015 - 05:42 PM

Nano is the future. A research team was working on senescent cell targeting silica nano-particles couple of years back, they are still developing them as far as I know.

But when I made this thread I was thinking more about stuff that's already FDA approved and could move from the lab to the clinic in a single day. In fact some of the things I posted in my original post are even synergistic, cyclodextrins can be used to enhance quercetin bio-availability.



#8 Kalliste

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Posted 31 March 2015 - 06:37 PM

Thyroid gland printed.

 

http://3dprint.com/5...-thyroid-mouse/

 

That would also seem pretty simple to do in humans except for the whole FDA issue.

 

I hope that the anti-anti-aging sentiment will begin to melt once people start putting these pieces togheter to see the whole picture.


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#9 niner

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Posted 31 March 2015 - 07:15 PM

At corb's request I changed the thread title from 'century' to 'decade'.   A century is certainly a long time, but the end of the decade will be here before we know it.  If the Methuselah Mouse Prize is still running, that might motivate some combination treatments.  I suspect that there is a lot of progress that will be made in senolytics, given the small number of compounds that were screened. 



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#10 corb

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Posted 31 March 2015 - 08:47 PM

Thanks for the fast reply niner.

 

Thyroid gland printed.

 

http://3dprint.com/5...-thyroid-mouse/

 

That would also seem pretty simple to do in humans except for the whole FDA issue.

 

I hope that the anti-anti-aging sentiment will begin to melt once people start putting these pieces togheter to see the whole picture.

 

Thyroid is great but thymus would've been much better for anti aging purposes.

The thymus can supposedly be regenerated by up-regulating a single gene, but gene therapy is decades from becoming mainstream medicine unfortunately.



#11 John Schloendorn

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Posted 31 March 2015 - 10:05 PM

I continue to think that LysoSENS enzymes discovered in the late 2000s (by Kemmish, Webb, Mathieu, Rebo myself...) would be the best shot at a near term clinical test of a component of "SENS proper" as proposed directly by Aubrey.  I guess I'm partially to blame that this didn't happen.  The world was kind of waiting for me to do it, but then I decided that I'd rather be needed in another branch of regenerative medicine (stem cells).  My true reasoning was that back then, I thought of myself as being better at basic discovery that most people, and most people were better at clinical testing than I was, so it would be rational to give it to other people to do the testing, while I go on to discover the next big thing.  Instead, my behavior seemed caused a meme like "well, if John with all his inside knowledge doesn't develop his own enzymes, then they've got to be somehow bad".  (I'm speculating, but think that was one element of it among others).  Ah well, unintended consequences.  Not sure what else I can do about it, other than alert people who like SENS things to be tested to the fact that multiple enzymes degrading arterial oxysterol and retinal lipofuscin, respectively continue to be available to go into regulated development, with a clearly predictable testing protocol, and then they either work or they don't.  All that's required is someone who can raise funds for biotech, and is willing to do the moderate work of engaging with contract clinical manufacturing & testing organizations.  


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#12 corb

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Posted 31 March 2015 - 11:37 PM

I continue to think that LysoSENS enzymes discovered in the late 2000s (by Kemmish, Webb, Mathieu, Rebo myself...) would be the best shot at a near term clinical test of a component of "SENS proper" as proposed directly by Aubrey.  I guess I'm partially to blame that this didn't happen.  The world was kind of waiting for me to do it, but then I decided that I'd rather be needed in another branch of regenerative medicine (stem cells).  My true reasoning was that back then, I thought of myself as being better at basic discovery that most people, and most people were better at clinical testing than I was, so it would be rational to give it to other people to do the testing, while I go on to discover the next big thing.  Instead, my behavior seemed caused a meme like "well, if John with all his inside knowledge doesn't develop his own enzymes, then they've got to be somehow bad".  (I'm speculating, but think that was one element of it among others).  Ah well, unintended consequences.  Not sure what else I can do about it, other than alert people who like SENS things to be tested to the fact that multiple enzymes degrading arterial oxysterol and retinal lipofuscin, respectively continue to be available to go into regulated development, with a clearly predictable testing protocol, and then they either work or they don't.  All that's required is someone who can raise funds for biotech, and is willing to do the moderate work of engaging with contract clinical manufacturing & testing organizations.  

 

Beta cyclodextrins are already in a human trial for genetic disorders which result in cholesterol accumulation.

And it seems the researcher who did the experiment with cyclodextrins and lipofuscin wants to move on to an in vivo animal study and is looking into compounds that can be synergistic with it for lipofuscin break down. So the ball might be back in your hands again.



#13 corb

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Posted 06 April 2015 - 10:12 PM

I found an interesting patent:
 

BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1. illustrates digestion of atherosclerotic plaques after exposure to different concentrations of a mixture of type I, III, IV, and V collagenases at 37 degrees Celsius and pH 7.4. The optimal concentration for digestion at 2- and 4-hour time points is 2 mg/ml, but all concentrations were able to fully digest the plaques by 24 hours.
FIG. 2. illustrates digestion of atherosclerotic plaques after exposure to different combinations of EDTA (1 mg/ml), (β-cyclodextrin (Cyclo, 10 mMol), tPA (1 mg/ml) and Collagenase mixture type I, III, IV, V (Col, 2 mg/ml) at 37 degrees Celsius, 225 rpm agitation, and ph 7.4. The first combination (#1) consisted of all four reagents together at once. The second combination (#2) consisted of EDTA, {β-cyclodextrin, and tPA together, with removal of this solution at 1 hour, and then addition of the collagenase mixture. The third combination (#3) consisted of all four agents together at once, followed by removal of the solution at 1 hour, and then addition of the collagenase mixture. The most effective combination was #2 at 4 hours, though #3 was effective as well.

 

http://patentimages....0801-D00001.png

 

http://www.google.co...s/US20130195828



#14 Logic

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Posted 07 April 2015 - 02:13 AM

The thymus can supposedly be regenerated by up-regulating a single gene, but gene therapy is decades from becoming mainstream medicine unfortunately.

 

Nope!  :)

You can go to Mexico and get injected with a made to order modified virus tomorrow if you like:

http://www.longecity...rapy-available/



#15 corb

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Posted 07 April 2015 - 10:54 PM

Nope!   :)

You can go to Mexico and get injected with a made to order modified virus tomorrow if you like:

http://www.longecity...rapy-available/

 

Well if they could safely insert the human analogue of that gene and use the same compound used in the mouse experiment to activate it on demand, then they should probably get on it. An adaptive immune system working at maximum capacity can potentially slow down aging a lot without any other significant genetic tune up. Long telomeres are nice but there has to be something in need of long telomeres in the first place. They're kinda going at it bottom up imho but, it's also the most popular thing so I can't blame them. If it gets them funds for more research, meh why not.

 

I just hope they don't get shut down like similar outfits we had running in Europe.



#16 Logic

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Posted 08 April 2015 - 01:11 AM

Well if they could safely insert the human analogue of that gene and use the same compound used in the mouse experiment to activate it on demand, then they should probably get on it. An adaptive immune system working at maximum capacity can potentially slow down aging a lot without any other significant genetic tune up. Long telomeres are nice but there has to be something in need of long telomeres in the first place. They're kinda going at it bottom up imho but, it's also the most popular thing so I can't blame them. If it gets them funds for more research, meh why not.
 
I just hope they don't get shut down like similar outfits we had running in Europe.


Telomerase and myostatin blocking are popular which is why they are mentioned in the article.

But 'made to order GMVs are also mentioned, so it may be worth talking to them to find out.

 

GMVs are used in lab rats all the time nowadays, so I agree that the tech is mature.

I also have no doubt that the FDA would rather get a BJ from a rabid crocodile than put their stamp of approval on something this effective and unintrusive.  ie: unprofitable.

:)

 

I too don't understand SENS's reluctance to embrace and advertise currently available longevity tech?

 



#17 Kalliste

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Posted 08 April 2015 - 04:27 AM

 

Well if they could safely insert the human analogue of that gene and use the same compound used in the mouse experiment to activate it on demand, then they should probably get on it. An adaptive immune system working at maximum capacity can potentially slow down aging a lot without any other significant genetic tune up. Long telomeres are nice but there has to be something in need of long telomeres in the first place. They're kinda going at it bottom up imho but, it's also the most popular thing so I can't blame them. If it gets them funds for more research, meh why not.
 
I just hope they don't get shut down like similar outfits we had running in Europe.


Telomerase and myostatin blocking are popular which is why they are mentioned in the article.

But 'made to order GMVs are also mentioned, so it may be worth talking to them to find out.

 

GMVs are used in lab rats all the time nowadays, so I agree that the tech is mature.

I also have no doubt that the FDA would rather get a BJ from a rabid crocodile than put their stamp of approval on something this effective and unintrusive.  ie: unprofitable.

:)

 

I too don't understand SENS's reluctance to embrace and advertise currently available longevity tech?

 

 

You dont? Take a minute to realize how hostile society is to new technology when it does not work. Remember Gelsinger and the gene-tech debacle of the late 90's? I remember some morons on the radio full of mythical stupor about the splendidness of mother nature and the evil wicked horrors of gene-tech who openly advocated all out bans of gene-editing due to this.

 

 

Jesse Gelsinger
From Wikipedia, the free encyclopedia
 
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Jesse Gelsinger (June 18, 1981 – September 17, 1999) was the first person publicly identified as having died in a clinical trial for gene therapy. He was 18 years old. Gelsinger suffered from ornithine transcarbamylase deficiency, an X-linked genetic disease of the liver, the symptoms of which include an inability to metabolize ammonia – a byproduct of protein breakdown. The disease is usually fatal at birth, but Gelsinger had not inherited the disease; in his case it was apparently the result of a spontaneous genetic mutation after conception and as such was not as severe – some of his cells were normal, enabling him to survive on a restricted diet and special medications.

Gelsinger joined a clinical trial run by the University of Pennsylvania that aimed at developing a treatment for infants born with severe disease. On September 13, 1999, Gelsinger was injected with an adenoviral vector carrying a corrected gene to test the safety of the procedure. He died four days later, September 17, at 2:30 pm, apparently having suffered a massive immune response triggered by the use of the viral vector used to transport the gene into his cells, leading to multiple organ failure and brain death.

A Food and Drug Administration (FDA) investigation concluded that the scientists involved in the trial, including the co-investigator Dr. James M. Wilson (Director of the Institute for Human Gene Therapy), broke several rules of conduct:

  • Inclusion of Gelsinger as a substitute for another volunteer who dropped out, despite Gelsinger's having high ammonia levels that should have led to his exclusion from the trial;
  • Failure by the university to report that two patients had experienced serious side effects from the gene therapy;
  • Failure to disclose, in the informed-consent documentation, the deaths of monkeys given a similar treatment.

The University of Pennsylvania later issued a rebuttal,[1] but paid the parents an undisclosed amount in settlement. Both Wilson and the University are reported to have had financial stakes in the research.[2][3] The Gelsinger case was a severe setback for scientists working in the field.[4]

 


Edited by Cosmicalstorm, 08 April 2015 - 04:28 AM.

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#18 Logic

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Posted 08 April 2015 - 08:44 AM

Good point Cosmicalstorm.  :)

 

What would be some proven, if not hugely effective, life extension therapies or protocols other than CR?

 

http://www.longecity...ongevity-drugs/

 



#19 niner

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Posted 08 April 2015 - 07:20 PM

What would be some proven, if not hugely effective, life extension therapies or protocols other than CR?

 

There's some human data for Metformin and Actonel.  Probably also for Rapamycin, though the populations using that are a lot smaller.  There are epidemiological associations with longevity for various foods, like olive oil, nuts, and green tea.  None of these have anything to do with SENS, though.



#20 corb

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Posted 17 April 2015 - 08:47 PM

https://www.youtube....h?v=3LpZzcCBLe0

https://www.youtube....h?v=mJqnO_kNHCU

 

SENSF released two introductory videos today. One for OncoSENS and one for MitoSENS.

I hope they go more in-depth and up to date after they finish introducing everything they're proposing, because these (first two) videos seem to be based on the state of research from a decade ago and aging research hasn't stood in place in the meantime.


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#21 Avatar of Horus

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Posted 23 April 2015 - 10:29 AM

Thanks for the fast reply niner.

 

Thyroid gland printed.

 

http://3dprint.com/5...-thyroid-mouse/

 

That would also seem pretty simple to do in humans except for the whole FDA issue.

 

I hope that the anti-anti-aging sentiment will begin to melt once people start putting these pieces togheter to see the whole picture.

 

Thyroid is great but thymus would've been much better for anti aging purposes.

The thymus can supposedly be regenerated by up-regulating a single gene, but gene therapy is decades from becoming mainstream medicine unfortunately.

 

IMHO one doesn't necessarily need gene therapy if the aim is regulating genes, since there are endogenous mechanisms for this, so this depends on the goal and context. Which gene is it BTW? (I have a guess, and I am asking because I intend to write about it in another topic soon that may be of more general interest.)

But gene regulation of endogenous genes is not SENS, because its cornerstone (and of the damage theories) is that aging results from the byproducts of the body's natural processes; so actually it is the opposite of it.



#22 corb

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Posted 23 April 2015 - 03:55 PM

IMHO one doesn't necessarily need gene therapy if the aim is regulating genes, since there are endogenous mechanisms for this, so this depends on the goal and context. Which gene is it BTW? (I have a guess, and I am asking because I intend to write about it in another topic soon that may be of more general interest.)

But gene regulation of endogenous genes is not SENS, because its cornerstone (and of the damage theories) is that aging results from the byproducts of the body's natural processes; so actually it is the opposite of it.

 

FOXN1

 

I'd say on general you are right upregulation of genes isn't SENS.

On the other hand when it comes to the thymus which just like the brain arrests regeneration incredibly early in life around the time we enter puberty, so by the time we're in our thirties the thymus is already very aged, by the time we're in our fifties it's more of a clump of fatty tissue than an organ of the lymphatic system, it doesn't age at the same rate as most other organs. I consider it an exception.
 


Edited by corb, 23 April 2015 - 03:57 PM.

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#23 Avatar of Horus

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Posted 21 May 2015 - 03:31 PM

 

IMHO one doesn't necessarily need gene therapy if the aim is regulating genes, since there are endogenous mechanisms for this, so this depends on the goal and context. Which gene is it BTW? (I have a guess, and I am asking because I intend to write about it in another topic soon that may be of more general interest.)

But gene regulation of endogenous genes is not SENS, because its cornerstone (and of the damage theories) is that aging results from the byproducts of the body's natural processes; so actually it is the opposite of it.

 

FOXN1

 

I'd say on general you are right upregulation of genes isn't SENS.

On the other hand when it comes to the thymus which just like the brain arrests regeneration incredibly early in life around the time we enter puberty, so by the time we're in our thirties the thymus is already very aged, by the time we're in our fifties it's more of a clump of fatty tissue than an organ of the lymphatic system, it doesn't age at the same rate as most other organs. I consider it an exception.
 

 

To what degree it is an exception, that is one of the most important currently unknown questions of the aging research.

 

Yes, the FOXN1, here is the post I was talking about, which also describes the upstream endogenous deregulation, in the second part under the thymus section, and also puts this into a wider context of aging, by also discussing other connected "exceptions":

from the Creating a unified theory of aging - Aging Theories - LONGECITY topic:
http://www.longecity...ndpost&p=728832


Edited by Avatar of Horus, 21 May 2015 - 03:31 PM.

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#24 Steve H

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Posted 21 May 2015 - 09:11 PM

If you want to use endogenous  systems to regulate genes you might get away with rejuvenating using TERT to lengthen telomeres and try to re-program the cells phentotype using the telomeres effect on gene expression via the TPE mechanism. Personally I feel a lot of problems could be resolved simply by going this path and trying to epigentically change things upstream of pathways like FOXN1 and GDF-11 etc... It wont fix everything but there is certainly a possibility of rejuvenation as has been seen in every animal study and on every human tissue it has been tested on. Will it work on humans? Only one way to find out and then see how much it fixes (if anything) before seeing what else needs repair. I believe it could potentially restore the endocrine system in which case the body will begin secreting youthful signals again on its own accord. Only one way to find out though as I say.

 

Stuff like stiffening of blood vessels, AGE and other cellular junk is unlikely to be fixed but its a start.

 



#25 2525

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Posted 08 June 2015 - 07:10 PM

It will be highly beneficial for Aubrey de Grey and SENS to let few volunteers who know web design

to redesign the SENS website and to bring it to 2015.

 

The reason is that other websites, with far much more trivial motivations or goals, they get millions of

dollars in donations simply because they made it so very easy to donate:

 

For example take a look at www.michaeljfox.org how smooth is the navigation on the website,

how clear, and how almosy anywhere you click, it takes you to a simple donation page

 

SENS would get millions of dollars in donations if only they would redesign 

the website to the standards of minimalism and clarity of 2015


Edited by 2525, 08 June 2015 - 07:11 PM.

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#26 niner

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Posted 08 June 2015 - 09:11 PM

I don't agree.  I went to the Michael J. Fox site, checked that out, went to sens.org, compared the two.  They are about equivalent in terms of cleanliness of design and navigation.  They both have a colorful 'donate' thingy that shows up all the time.  The MJF donate thingy is slightly larger and is offset to make it more obvious.  That's great, but it's not millions of dollars in new donations great.


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#27 sthira

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Posted 08 June 2015 - 09:51 PM

A SENS mobile site option would make it easier for those of us without laptops.

#28 alc

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Posted 23 June 2015 - 03:01 AM

It will be highly beneficial for Aubrey de Grey and SENS to let few volunteers who know web design

to redesign the SENS website and to bring it to 2015.

 

The reason is that other websites, with far much more trivial motivations or goals, they get millions of

dollars in donations simply because they made it so very easy to donate:

 

For example take a look at www.michaeljfox.org how smooth is the navigation on the website,

how clear, and how almosy anywhere you click, it takes you to a simple donation page

 

SENS would get millions of dollars in donations if only they would redesign 

the website to the standards of minimalism and clarity of 2015

 

@ 2525 - there are/were lots of similar comments with yours, however SENS/FA and some people, downplay all these comments. They are not open to accept that indeed things needs to change in order for them to advance with the donations/funding. Switching to "for profit" will really accelerate their development, however they downplay that all the time and want to stick with a foundation type. Therefore the struggle with donations and the frustration that gets in the way of research - and I know that is really depressing. However they are not listening to any good suggestions and they have a "business" model that is stuck in '90s.

 

By the comments some people make to defend them, you realize that those people have never been involved in large companies and understand how funding is secured. They believe that just presenting good ideas is enough. Unfortunatelly the world we live in is absurd, and even SENS (or others similar to them) wants to cure aging, rich people, preffer to die with the money in their pocket instead of funding cutting edge R&D that SENS and others do.

 

On the other hand, SENS is facing a credibility issue, and instead of cutting the Gordian knot, they keep walk same path. The problem is that - using an analogy ... something they like - they want to send people, not to the Moon, not to Mars, not to next solar system, but across the galaxy and bring those people back safely ... and all this, without having the proof that they can send somebody to Earth's orbit and back ... therefore 99.999% of people who look at them don't believe them right away. Honestly, I think they can send somebody back and forth across galaxy without doing regular orbit launching. However, to secure the huge funds for such effort, they have to be pragmatical and make a proof of concept: one of their Strategies needs to be showcased and literally show it will work in humans (NOT mouse models). There is an opportunity with senescent cells ...

 

But again, these ideas were mentioned numerous times, and I got tired, others got tired, to keep asking same thing.

 

Let them do the way they like it ... and in two centuries they will reach somewhere ... meanwhile, others more pragmatical will cut it to the chase.

 

Nota Bene: I do not post to start a flaming war, so whoever wants to give me "two thumbs down" is welcome, but before they do it, please analyze things mentioned here and ask yourself why so many people, comming from various fields suggest the same thing again, and again, and again ... look here, look @ FA, look on similar forums.


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#29 eternaltraveler

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Posted 08 July 2015 - 12:09 AM

I continue to think that LysoSENS enzymes discovered in the late 2000s (by Kemmish, Webb, Mathieu, Rebo myself...) would be the best shot at a near term clinical test of a component of "SENS proper" as proposed directly by Aubrey.  I guess I'm partially to blame that this didn't happen.  The world was kind of waiting for me to do it, but then I decided that I'd rather be needed in another branch of regenerative medicine (stem cells).  My true reasoning was that back then, I thought of myself as being better at basic discovery that most people, and most people were better at clinical testing than I was, so it would be rational to give it to other people to do the testing, while I go on to discover the next big thing.  Instead, my behavior seemed caused a meme like "well, if John with all his inside knowledge doesn't develop his own enzymes, then they've got to be somehow bad".  (I'm speculating, but think that was one element of it among others).  Ah well, unintended consequences.  Not sure what else I can do about it, other than alert people who like SENS things to be tested to the fact that multiple enzymes degrading arterial oxysterol and retinal lipofuscin, respectively continue to be available to go into regulated development, with a clearly predictable testing protocol, and then they either work or they don't.  All that's required is someone who can raise funds for biotech, and is willing to do the moderate work of engaging with contract clinical manufacturing & testing organizations.  

 

My feelings regarding the senescent T cell scrubber that we also made back then mirror yours on the LysoSENS enzymes (which I also agree with).  At the time It seemed that the filter was in the early preclinical development of technologies which would then be carried along by others after the principles were proven.  Now it seems to me that if you want something done you need to carry it all the way from basic science to the bedside yourself.  As it turns out the prime thing almost everyone does, is nothing at all.  If you want something to happen you have to do all of it.

 

Lesson learned.


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